Exploratory data on the clinical efficacy of monoclonal antibodies against SARS-CoV-2 Omicron variant of concern
- Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, Italy
- Infectious Disease Unit, Padova University Hospital, Italy
- Infectious Diseases Division, Department of Medicine, University of Udine and Azienda Sanitaria Universitaria Friuli Centrale, Italy
- Section of Clinical Biochemistry, Department of Neuroscience, Biomedicine and Movement, University of Verona, Italy
- Microbiology and Virology Unit, Department of Diagnostics and Public Health, University of Verona, Italy
- Viral genomics and transcriptomics Laboratory, Istituto Zooprofilattico Sperimentale delle Venezie, Italy
- Direzione Farmaceutico, Protesica, Dispositivi Medici, Regione del Veneto, Italy
- Italian Medicines Agency, Italy
Figures
Figure 1
Flow diagram of the progress through the phases of the MANTICO trial according to the CONSORT statement.
Figure 2
Time to symptom resolution by type of treatment in the study population infected with Delta (A) and Omicron (B).
Tables
Table 1
Baseline characteristics of the overall study population by type of variant of concern.
| Characteristic | DeltaN=141 | OmicronN=170 | p value |
|---|---|---|---|
| Sex (male) – n (%) | 69 (48.94) | 101 (59.41) | 0.068 |
| Age – median (IQR) (range) | 65.7 (15.4) (50–92) | 64.5 (14.8) (50–90) | 0.585 |
| Smoking status – n (%) | |||
| Smoker | 8 (5.67) | 24 (14.12) | 0.015 |
| Former smoker | 32 (22.70) | 28 (16.47) | 0.194 |
| Non-smoker | 101 (71.63) | 118 (69.41) | 0.709 |
| BMI – n (%) | |||
| ≤29 | 101 (71.63) | 132 (77.65) | 0.239 |
| ≥30 | 40 (28.37) | 38 (22.35) | 0.239 |
| SARS-CoV-2 serological status – n (%) | |||
| Antibody-positive | 70 (49.65) | 134 (78.82) | <0.001 |
| Antibody-negative | 68 (48.23) | 35 (20.59) | <0.001 |
| Other | 3 (2.13) | 1 (0.59) | |
| Anti-SARS-CoV-2 vaccination status – n (%) | |||
| 3 doses or 2 doses ≤120 days | 23 (16.31) | 66 (38.82) | <0.001 |
| 1 or 2 doses ≥120 days or not vaccinated | 113 (80.14) | 99 (58.24) | <0.001 |
| Other | 5 (3.55) | 5 (2.94) | |
| Comorbidities – n (%) | |||
| Diabetes | 3 (2.13) | 6 (3.53) | 0.519 |
| Cardiovascular disease | 56 (39.72) | 61 (35.88) | 0.557 |
| Chronic kidney disease | 7 (4.96) | 9 (5.29) | 1.000 |
| Chronic liver disease | 3 (2.13) | 12 (7.06) | 0.061 |
| Chronic pulmonary disease | 16 (11.35) | 33 (19.41) | 0.061 |
| Immunocompromising conditions | 17 (12.06) | 35 (20.59) | 0.048 |
| Symptoms at enrolment – n (%) | |||
| Cough | 96 (68.09) | 118 (69.41) | 0.807 |
| Nasal congestion | 69 (48.94) | 69 (40.59) | 0.169 |
| Sore throat | 32 (22.70) | 69 (40.59) | 0.001 |
| Feeling hot or feverish | 103 (73.05) | 99 (58.24) | 0.008 |
| Myalgia | 46 (32.62) | 54 (31.76) | 0.903 |
| Fatigue | 47 (33.33) | 75 (44.12) | 0.062 |
| Headache | 59 (41.84) | 60 (35.29) | 0.244 |
| Anosmia/ageusia | 39 (27.66) | 4 (2.35) | <0.001 |
| Nausea/vomiting | 28 (19.86) | 11 (6.47) | <0.001 |
| Diarrhoea | 15 (10.64) | 12 (7.06) | 0.314 |
| Serum C-reactive protein level – n | 136 | 161 | |
| Mean (SD), mg/L | 20.58 (29.00) | 14.29 (21.72) | 0.022 |
Table 2
Bivariate Cox regression of symptom resolution predictors by type of variant of concern.
| Delta | Omicron | |||
|---|---|---|---|---|
| Predictor | HR (95% CI) | p value | HR (95% CI) | p value |
| Gender | 0.80 (0.57–1.11) | 0.182 | 0.84 (0.61–1.14) | 0.257 |
| Age | 1.00 (0.98–1.02) | 0.952 | 1.00 (0.98–1.01) | 0.626 |
| BMI | 1.03 (0.72–1.50) | 0.855 | 1.17 (0.82–1.68) | 0.393 |
| SARS-CoV-2 serological status | 0.93 (0.67–1.31) | 0.690 | 0.82 (0.57–1.20) | 0.307 |
| Anti-SARS-CoV-2 vaccination status | 1.30 (0.83–2.04) | 0.257 | 0.91 (0.66–1.24) | 0.539 |
| Diabetes | 0.63 (0.34–1.18) | 0.150 | 1.19 (0.76–1.88) | 0.444 |
| Cardiovascular disease | 0.96 (0.69–1.35) | 0.831 | 0.85 (0.62–1.17) | 0.319 |
| Chronic kidney disease | 1.24 (0.58–2.66) | 0.581 | 1.12 (0.57–2.21) | 0.733 |
| Chronic liver disease | 2.42 (0.76–7.68) | 0.135 | 1.33 (0.74–2.40) | 0.341 |
| Chronic pulmonary disease | 0.78 (0.46–1.31) | 0.346 | 0.98 (0.67–1.43) | 0.902 |
| Immunocompromising conditions | 1.00 (0.60–1.66) | 0.989 | 0.80 (0.55–1.17) | 0.252 |
Table 3
Baseline characteristics of the study population infected with Delta by type of treatment.
| Characteristic | TotalN=141 | SotrovimabN=43 | Bamlanivimab/etesevimabN=48 | Casirivimab/imdevimabN=50 |
|---|---|---|---|---|
| Sex (male) – n (%) | 69 (48.94) | 22 (51.16) | 21 (43.75) | 26 (52.00) |
| Age – median (IQR) (range) | 65.7 (15.4) (50–92) | 65.8 (16.4) (50–90) | 68.6 (11.8) (50–92) | 63.2 (12) (50–89) |
| Smoking status – n (%) | ||||
| Smoker | 8 (5.67) | 2 (4.65) | 4 (8.33) | 2 (4.00) |
| Former smoker | 32 (22.70) | 8 (18.60) | 11 (22.92) | 13 (26.00) |
| Non-smoker | 101 (71.63) | 33 (76.74) | 33 (68.75) | 35 (70.00) |
| BMI – n (%) | ||||
| ≤29 | 101 (71.63) | 29 (67.44) | 36 (75.00) | 36 (72.00) |
| ≥30 | 40 (28.37) | 14 (32.56) | 12 (25.00) | 14 (28.00) |
| SARS-CoV-2 serological status – n (%) | ||||
| Antibody-positive | 70 (49.65) | 20 (46.51) | 29 (61.70) | 21 (43.75) |
| Antibody-negative | 68 (48.23) | 23 (53.49) | 18 (38.30) | 27 (56.25) |
| Other | 3 (2.13) | 0 | 1 (2.08) | 2 (4.00) |
| Anti-SARS-CoV-2 vaccination status – n (%) | ||||
| 3 doses | 16 (11.35) | 6 (13.95) | 3 (6.25) | 7 (14.00) |
| 2 doses ≤120 days | 7 (4.96) | 2 (4.65) | 2 (4.17) | 3 (6.00) |
| 1 or 2 doses ≥120 days | 54 (38.30) | 14 (32.56) | 26 (54.17) | 14 (28.00) |
| Not vaccinated | 59 (41.84) | 19 (44.19) | 15 (31.25) | 25 (50.00) |
| Other | 5 (3.55) | 2 (4.65) | 2 (4.17) | 1 (2.00) |
| Comorbidities – n (%) | ||||
| Diabetes | 3 (2.13) | 0 | 2 (4.17) | 1 (2.00) |
| Cardiovascular disease | 56 (39.72) | 18 (41.86) | 20 (41.67) | 18 (36.00) |
| Chronic kidney disease | 7 (4.96) | 1 (2.33) | 2 (4.17) | 4 (8.00) |
| Chronic liver disease | 3 (2.13) | 0 | 1 (2.08) | 2 (4.00) |
| Chronic pulmonary disease | 16 (11.35) | 6 (13.95) | 4 (8.33) | 6 (12.00) |
| Immunocompromising conditions | 17 (12.06) | 6 (13.95) | 6 (12.50) | 5 (10.00) |
| Symptoms at enrolment – n (%) | ||||
| Cough | 96 (68.09) | 28 (65.12) | 36 (75.00) | 32 (64.00) |
| Nasal congestion | 69 (48.94) | 20 (46.51) | 22 (45.83) | 27 (54.00) |
| Sore throat | 32 (22.70) | 10 (23.26) | 8 (16.67) | 14 (28.00) |
| Feeling hot or feverish | 103 (73.05) | 31 (72.09) | 36 (75.00) | 36 (72.00) |
| Myalgia | 46 (32.62) | 11 (25.58) | 16 (33.33) | 19 (38.00) |
| Fatigue | 47 (33.33) | 13 (30.23) | 15 (31.25) | 19 (38.00) |
| Headache | 59 (41.84) | 15 (34.88) | 15 (31.25) | 29 (58.00) |
| Anosmia/ageusia | 39 (27.66) | 12 (27.91) | 15 (31.25) | 12 (24.00) |
| Nausea/vomiting | 28 (19.86) | 6 (13.95) | 9 (18.75) | 13 (26.00) |
| Diarrhoea | 15 (10.64) | 1 (2.33) | 5 (10.42) | 9 (18.00) |
| Serum C-reactive protein level – n | 136 | 41 | 46 | 49 |
| Mean (SD), mg/L | 20.58 (29.00) | 22.84 (33.70) | 25.27 (34.20) | 14.29 (15.99) |
Table 4
Efficacy outcomes of the study population infected with Delta by type of treatment with the exclusion of time to sustained patient-reported symptom resolution.
| Outcome | TotalN=141 | SotrovimabN=44 | Bamlanivimab/etesevimabN=47 | Casirivimab/imdevimabN=50 |
|---|---|---|---|---|
| Composite primary outcome – n (%) | 0 | 0 | 0 | 0 |
| Hospitalisation | 0 | 0 | 0 | 0 |
| Need of supplemental oxygen therapy | 0 | 0 | 0 | 0 |
| Death from any cause through day 14 | 0 | 0 | 0 | 0 |
| Secondary outcomes | ||||
| Emergency department visits through day 28 – n (%) | 1 (0.71) | 0 | 0 | 1 (2) |
| All-cause mortality through day 28 – n (%) | 0 | 0 | 0 | 0 |
| Duration of supplemental oxygen therapy – days | 0 | 0 | 0 | 0 |
| Rate of non-invasive ventilation – n (%) | 0 | 0 | 0 | 0 |
| Duration of non-invasive ventilation – days | 0 | 0 | 0 | 0 |
| Rate of mechanical ventilation – n (%) | 0 | 0 | 0 | 0 |
| Duration of mechanical ventilation – days | 0 | 0 | 0 | 0 |
Table 5
Baseline characteristics of the study population infected with Omicron by type of treatment.
| Characteristic | TotalN=170 | SotrovimabN=61 | Bamlanivimab/etesevimabN=57 | Casirivimab/imdevimabN=52 |
|---|---|---|---|---|
| Sex (male) – n (%) | 101 (59.41) | 36 (59.02) | 30 (52.63) | 35 (67.31) |
| Age – median (IQR) (range) | 64.5 (14.8) (50–90) | 64.2 (15) (50–90) | 64.8 (14.6) (50–86) | 65.3 (14.8) (50–86) |
| Smoking status – n (%) | ||||
| Smoker | 24 (14.12) | 6 (9.84) | 11 (19.30) | 7 (13.46) |
| Former smoker | 28 (16.47) | 9 (14.75) | 11 (19.30) | 8 (15.38) |
| Non-smoker | 118 (69.41) | 46 (75.41) | 35 (61.40) | 37 (71.15) |
| BMI – n (%) | ||||
| ≤29 | 132 (77.65) | 53 (86.89) | 42 (73.68) | 37 (71.15) |
| ≥30 | 38 (22.35) | 8 (13.11) | 15 (26.32) | 15 (28.85) |
| SARS-CoV-2 serological status – n (%) | ||||
| Antibody-positive | 134 (78.82) | 45 (73.77) | 45 (78.95) | 44 (84.62) |
| Antibody-negative | 35 (20.59) | 16 (26.23) | 11 (19.30) | 8 (15.38) |
| Other | 1 (0.59) | 0 | 1 (1.75) | 0 |
| Anti-SARS-CoV-2 vaccination status – n (%) | ||||
| 3 doses | 62 (36.47) | 24 (39.34) | 19 (33.33) | 19 (36.54) |
| 2 doses ≤120 days | 4 (2.35) | 2 (3.28) | 1 (1.75) | 1 (1.92) |
| 1 or 2 doses ≥120 days | 57 (33.53) | 16 (26.23) | 22 (38.60) | 19 (36.54) |
| Not vaccinated | 42 (24.71) | 18 (29.51) | 13 (22.81) | 11 (21.15) |
| Other | 5 (2.94) | 1 (1.64) | 2 (3.51) | 2 (3.85) |
| Comorbidities – n (%) | ||||
| Diabetes | 6 (3.53) | 2 (3.28) | 2 (3.51) | 2 (3.85) |
| Cardiovascular disease | 61 (35.88) | 18 (29.51) | 17 (29.82) | 26 (50.00) |
| Chronic kidney disease | 9 (5.29) | 4 (6.56) | 2 (3.51) | 3 (5.77) |
| Chronic liver disease | 12 (7.06) | 4 (6.56) | 5 (8.77) | 3 (5.77) |
| Chronic pulmonary disease | 33 (19.41) | 11 (18.03) | 15 (26.32) | 7 (13.46) |
| Immunocompromising conditions | 35 (20.59) | 15 (24.59) | 11 (19.30) | 9 (17.31) |
| Symptoms at enrolment – n (%) | ||||
| Cough | 118 (69.41) | 42 (68.85) | 37 (64.91) | 39 (75.00) |
| Nasal congestion | 69 (40.59) | 28 (45.90) | 25 (43.86) | 16 (30.77) |
| Sore throat | 69 (40.59) | 22 (36.07) | 27 (47.37) | 20 (38.46) |
| Feeling hot or feverish | 99 (58.28) | 37 (60.66) | 32 (56.14) | 30 (57.69) |
| Myalgia | 54 (31.76) | 20 (32.79) | 18 (31.58) | 16 (30.77) |
| Fatigue | 75 (44.12) | 31 (50.82) | 20 (35.09) | 24 (46.15) |
| Headache | 60 (35.29) | 23 (37.70) | 20 (35.09) | 17 (32.69) |
| Anosmia/ageusia | 4 (2.35) | 1 (1.64) | 2 (3.51) | 1 (1.92) |
| Nausea/vomiting | 11 (6.47) | 4 (6.56) | 5 (8.77) | 2 (3.85) |
| Diarrhoea | 12 (7.06) | 5 (8.20) | 4 (7.02) | 3 (5.77) |
| Serum C-reactive protein level – n | 161 | 57 | 56 | 48 |
| Mean (SD), mg/L | 14.29 (21.72) | 12.65 (15.97) | 17.19 (31.07) | 12.87 (12.55) |
Table 6
Efficacy outcomes of the study population infected with Omicron by type of treatment with the exclusion of time to sustained patient-reported symptom resolution.
| Outcome | TotalN=170 | SotrovimabN=61 | Bamlanivimab/etesevimabN=57 | Casirivimab/imdevimabN=52 |
|---|---|---|---|---|
| Composite primary outcome – n (%) | 2 (1.18) | 0 | 2 (3.51) | 0 |
| Hospitalisation | 2 (1.18) | 0 | 2 (3.51) | 0 |
| Need of supplemental oxygen therapy | 2 (1.18) | 0 | 2 (3.51) | 0 |
| Death from any cause through day 14 | 1 (0.59) | 0 | 1 (1.75) | 0 |
| Secondary outcomes | ||||
| Emergency department visits through day 28 – n (%) | 1 (0.59) | 0 | 1 (1.75) | 0 |
| All-cause mortality through day 28 – n (%) | 2 (1.18) | 0 | 2 (3.51) | 0 |
| Duration of supplemental oxygen therapy – days | 4 (patient 1) 22 (patient 2) | 0 | 4 (patient 1) 22 (patient 2) | 0 |
| Rate of non-invasive ventilation – n (%) | 2 (1.18) | 0 | 2 (3.51) | 0 |
| Duration of non-invasive ventilation – days | 4 (patient 1) 13 (patient 2) | 0 | 4 (patient 1) 13 (patient 2) | 0 |
| Rate of mechanical ventilation – n (%) | 0 | 0 | 0 | 0 |
| Duration of mechanical ventilation – days | 0 | 0 | 0 | 0 |
Table 7
Cox regression to assess the difference between treatment effects upon the time to symptom resolution in selected subgroups of interest in the study population infected with Omicron.
| Subgroup | Sotrovimab | Bamlanivimab/etesevimab | Casirivimab/imdevimab | ||
|---|---|---|---|---|---|
| HR | HR (95% CI) | p value | HR (95% CI) | p value | |
| SARS-CoV-2 serological status | |||||
| Antibody-negative | 1 | 0.34 (0.16–0.75) | 0.008 | 0.41 (0.18–0.97) | 0.043 |
| Antibody-positive | 1 | 0.40 (0.22–0.71) | 0.002 | 0.32 (0.18–0.57) | <0.001 |
| Anti-SARS-CoV-2 vaccination status | |||||
| 1 or 2 doses ≥120 days or not vaccinated | 1 | 0.47 (0.30–0.77) | 0.003 | 0.49 (0.30–0.82) | 0.006 |
| 3 doses or 2 doses ≤120 days | 1 | 0.50 (0.28–0.89) | 0.019 | 0.35 (0.19–0.62) | <0.001 |
Additional files
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MDAR checklist
- https://cdn.elifesciences.org/articles/79639/elife-79639-mdarchecklist1-v1.pdf
-
Reporting standard 1
CONSORT checklist.
- https://cdn.elifesciences.org/articles/79639/elife-79639-repstand1-v1.doc
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Exploratory data on the clinical efficacy of monoclonal antibodies against SARS-CoV-2 Omicron variant of concern
eLife 11:e79639.
https://doi.org/10.7554/eLife.79639
